Every US FDA ANDA or NDA application requires time and money to develop drugs that will enter the U.S. market. Imagine spending years to develop a drug then failing your pre-approval inspection. This result would be devastating and require more resources to obtain an approval. The pre-approval inspection is one of the last reviews of the drug approval process, so it is important that your team is aware of what is required to pass the pre-approval inspection. The pre-approval inspector (PAI) manager is the liaison between all parties.
The PAI manager will review applicant’s GMP history, FDA 483 observation forms, and schedules the pre-approval inspections. All ANDA FDA & NDA applicants will be required to comply with CGMPs. It is critical to have the quality management team confirm these procedures are being met. Any establishment listed in the application regardless of location may be inspected. All associated facilities such as contract labs and packagers should be listed on the application. Failure to do so can result in an FDA 483. The pharmaceutical company must verify conformance to the commitments listed on their ANDA or NDA application. Generic drugs must note on the application and prove bio-equivalence to the brand drug (NDA) for which it is compared. Since ANDA applicants are not required to replicate the expensive clinical trials that have been used in the original NDA, they can use a bio equivalency study to show the rate at which the body absorbs the drug and the efficacy and safety is equivalent.
US FDA NDA applicants should have all pre-clinical and clinical trial data available for review. All data presented must be accurate and authentic. Data that the FDA will want to review include laboratory records, batch records, product development report, and SOPs. In addition, the FDA inspector will ask to view laboratory testing of products including any evaluations of the analytical methodology and the adequacy within. Other items such as equipment qualification, change control and FDA correspondence will be on the FDA inspector’s list to review. After an extensive review of records and the facility inspection, the FDA inspector will give the results of the inspection to the applicant. If the applicant is unfortunate to receive an FDA 483 form, all items that must be addressed prior to drug approval will be listed. FDA 483 observations can range from lack of validated methods to the lack of data access/ storage procedures.
The inspector will ultimately recommend for approval of the drug or to withhold it. There are many reasons for withholding drug approvals. It is beneficial for the applicant to team up with a regulatory consulting group to prepare the firm for their pre-approval inspection. Biotech Research Group offers mock pre-approval inspections for clients wanting a detailed review of their data and facilities with feedback on their readiness to pass the pre-approval inspection.
Christina Sanchez Miller, MPH has over 20 years of management, biologics, quality assurance and research experience in the medical field. She is a published author in scientific books, papers and has presented at several international conferences. Christina has developed medical applications in the biologics field. Her experience includes operations and consulting in FDA Adverse Event Reporting, FDA Product Deviation Reporting, FDA 483’s, cGTP’s, infection control, certified ISO Class 5, 7, 8 development and maintenance, QIC and auditing.
BRG is a global scientific & regulatory consulting firm with extensive experience in the strategic development of drug products, biologics, medical devices, combination products and FDA regulatory affairs. BRG is a pharmaceutical consulting group focusing on NDA regulatory services, FDA ANDA submissions, and IND consulting services.
The opinions and statements in this blog are those of the authors and do not necessarily reflect those of BRG. This blog is based on personal experience and reviews of information publicly available or identified in other database searches.